Toll-like receptor 4/nuclear factor-κB signaling pathway is involved in ACTG-toxin H-mediated anti-inflammatory effect

Xinying Yang; Guojian Zhang; Xuelian Tang; Jieying Jiao; Sung Yeon Kim; Joo Young Lee; Tianjiao Zhu; Dehai Li; Yong Gab Yun; Qianqun Gu; Hyun Park

doi:10.1007/s11010-012-1502-9

Toll-like receptor 4/nuclear factor-κB signaling pathway is involved in ACTG-toxin H-mediated anti-inflammatory effect

Mol Cell Biochem. 2013 Feb;374(1-2):29-36. doi: 10.1007/s11010-012-1502-9. Epub 2012 Nov 9.

Authors

Xinying Yang¹, Guojian Zhang, Xuelian Tang, Jieying Jiao, Sung Yeon Kim, Joo Young Lee, Tianjiao Zhu, Dehai Li, Yong Gab Yun, Qianqun Gu, Hyun Park

Affiliation

¹ Department of Infection Biology, Zoonosis Research Center, Wonkwang University School of Medicine, Iksan, Jeonbuk, 570-749, South Korea.

PMID: 23139166
DOI: 10.1007/s11010-012-1502-9

Abstract

ACTG-toxin H (AH) originates from Alternaria sp. In this study, we explored the molecular mechanism underlying the anti-inflammatory properties of AH. Treatment with AH inhibited lipopolysaccharide (LPS)-induced interleukin-6, IL-1β, inducible nitric oxide synthase, and cyclooxygenase-2 expression and nitric oxide production. Furthermore, AH inhibited LPS-induced P38 MAPK and Akt activation in RAW264.7 cells. Electrophoretic mobility shift assays (EMSAs) showed that AH inhibited LPS-induced nuclear factor-κB (NFκB) DNA-binding activity. Using transfection assay and measurement of an NFκB-sensitive promoter region, we found that transfection of toll-like receptor 4 (TLR4) increased LPS-induced NFκB transcription activity in 293T cells. AH significantly blocked LPS-induced NFκB activation in TLR4-transfected cells. Taken together, our data indicated that anti-inflammatory properties of AH resulted from the inhibition of proinflammatory cytokines and enzyme production via the TLR4/NFκB signaling pathway.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alternaria / metabolism
Animals
Anti-Inflammatory Agents / pharmacology*
Cell Line
Cell Survival
Cyclooxygenase 2 / metabolism
DNA-Binding Proteins / metabolism
Enzyme Activation / drug effects
HEK293 Cells
Humans
Inflammation / immunology*
Interleukin-1beta / metabolism
Interleukin-6 / metabolism
Lipopolysaccharides
Macrophages / metabolism
Mice
Mycotoxins / pharmacology*
NF-kappa B / metabolism*
Nitric Oxide / biosynthesis
Nitric Oxide Synthase Type II / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Signal Transduction
Toll-Like Receptor 4 / genetics
Toll-Like Receptor 4 / metabolism*
p38 Mitogen-Activated Protein Kinases / metabolism

Substances

Anti-Inflammatory Agents
DNA-Binding Proteins
Interleukin-1beta
Interleukin-6
Lipopolysaccharides
Mycotoxins
NF-kappa B
Tlr4 protein, mouse
Toll-Like Receptor 4
Nitric Oxide
Nitric Oxide Synthase Type II
Cyclooxygenase 2
Proto-Oncogene Proteins c-akt
p38 Mitogen-Activated Protein Kinases